The broad objectives of the proposed project are to provide an understanding of the mechanisms that lead to sterol accumulation in human renal cancer cells, in order to develop new chemotherapeutic and diagnostic approaches to this disease. Because of lack of other meaningful models for the study of these tumors, the present research will be conducted on human renal cancer in culture. Over 40 such cell lines are available to us through our tumor bank and more will be available in the future from new surgical specimens. Some of the characteristics of sterol synthesis regulation and transport in cultured normal human kidney have already been described by the applicants. The present studies will attempt to compare characteristics of sterol uptake and excretion in normal and malignant kidney cells, as well as the characteristics of sterol synthesis, synthesis regulation and the nutritional requirements of these cells. The methodology to be used includes techniques of tissue culture, lipid chemistry, and enzymology. When most aspects of sterol synthesis and transport by human renal cancer cells are understood, it well may be possible to plan a rational chemotherapeutic attack to this disease. For example, if it is found that cholesterol accumulated by these cells in vivo is mainly exogenous in origin, it will be possible to develop a sterol-cytotoxic combination molecule that will selectively destroy these malignant cells.